title: Hypothermic modulation of cerebral ischemic injury during cardiopulmonary bypass in pigs.
abstract: BACKGROUND
  The aim of this study was to determine whether progressive levels of hypothermia (37, 34, 31, or 28 degrees C) during cardiopulmonary bypass (CPB) in pigs reduce the physiologic and metabolic consequences of global cerebral ischemia.
  
  
  METHODS
  Sagittal sinus and cortical microdialysis catheters were inserted into anesthetized pigs. Animals were placed on CPB and randomly assigned to 37 degrees C (n = 10), 34 degrees C (n = 10), 31 degrees C (n = 11), or 28 degrees C (n = 10) management. Next 20 min of global cerebral ischemia was produced by temporarily ligating the innominate and left subclavian arteries, followed by reperfusion, rewarming, and termination of CPB. Cerebral oxygen metabolism (CMRO2) was calculated by cerebral blood flow (radioactive microspheres) and arteriovenous oxygen content gradient. Cortical excitatory amino acids (EAA) by microdialysis were measured using high-performance liquid chromatography. Electroencephalographic (EEG) signals were graded by observers blinded to the protocol. After CPB, cerebrospinal fluid was sampled to test for S-100 protein and the cerebral cortex was biopsied.
  
  
  RESULTS
  Cerebral oxygen metabolism increased after rewarming from 28 degrees C, 31 degrees C, and 34 degrees C CPB but not in the 37 degrees animals; CMRO2 remained lower with 37 degrees C (1.8 +/- 0.2 ml x min[-1] x 100 g[-1]) than with 28 degrees C (3.1 +/- 0.1 ml x min[-1] x 100 g[-1]; P < 0.05). The EEG scores after CPB were depressed in all groups and remained significantly lower in the 37 degrees C animals. With 28 degrees C and 31 degrees C CPB, EAA concentrations did not change. In contrast, glutamate increased by sixfold during ischemia at 37 degrees C and remained significantly greater during reperfusion in the 34 degrees C and 37 degrees C groups. Cortical biopsy specimens showed no intergroup differences in energy metabolites except two to three times greater brain lactate in the 37 degrees C animals. S-100 protein in cerebrospinal fluid was greater in the 37 degrees C (6 +/- 0.9 microg/l) and 34 degrees C (3.5 +/- 0.5 microg/l) groups than the 31 degrees C (1.9 +/- 0.1 microg/l) and 28 degrees C (1.7 +/- 0.2 microg/l) animals.
  
  
  CONCLUSIONS
  Hypothermia to 28 degrees C and 31 degrees C provides significant cerebral recovery from 20 min of global ischemia during CPB in terms of EAA release, EEG and cerebral metabolic recovery, and S-100 protein release without greater advantage from cooling to 28 degrees C compared with 31 degrees C. In contrast, ischemia during 34 degrees C and particularly 37 degrees C CPB showed greater EAA release and evidence of neurologic morbidity. Cooling to 31 degrees C was necessary to improve acute recovery during global cerebral ischemia on CPB.
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, Galveston 77555-0591, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: Conroy
authors.forename: C Y
authors.initials: CY
authors.lastname: Lin
authors.forename: L W
authors.initials: LW
authors.lastname: Jenkins
authors.forename: D S
authors.initials: DS
authors.lastname: DeWitt
authors.forename: M H
authors.initials: MH
authors.lastname: Zornow
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: W E
authors.initials: WE
authors.lastname: Johnston
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002560:Cerebrovascular Circulation; D003080:Cold Temperature; D018846:Excitatory Amino Acids / Q000378:metabolism; D005260:Female; D006439:Hemodynamics; D007036:Hypothermia, Induced; D017551:Microdialysis; D008863:Microspheres; D012044:Regression Analysis; D013552:Swine
chemical_list: D018846:Excitatory Amino Acids